Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Фев. 28, 2022

Metabolic enzymes have an indispensable role in metabolic reprogramming, and their aberrant expression or activity has been associated with chemosensitivity. Hence, targeting remains attractive approach for treating tumors. However, the influence regulation of cysteine desulfurase (NFS1), a rate-limiting enzyme iron-sulfur (Fe-S) cluster biogenesis, colorectal cancer (CRC) remain elusive. Here, using vivo gene-based clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 library screen, we revealed that loss NFS1 significantly enhanced sensitivity CRC cells to oxaliplatin. In vitro results showed deficiency synergizing oxaliplatin triggered PANoptosis (apoptosis, necroptosis, pyroptosis, ferroptosis) by increasing intracellular levels reactive oxygen species (ROS). Furthermore, oxaliplatin-based oxidative stress phosphorylation level serine residues NFS1, which prevented S293 phosphorylation-dependent manner during treatment. addition, high transcriptionally regulated MYC, was found tumor tissues poor survival hyposensitivity chemotherapy patients CRC. Overall, findings this study provided insights into underlying mechanisms identified inhibition as promising strategy improving outcome platinum-based treatment

Язык: Английский

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New insights into the interplay between long non‐coding RNAs and RNA‐binding proteins in cancer

Cancer Communications, Год журнала: 2022, Номер 42(2), С. 117 - 140

Опубликована: Янв. 12, 2022

Abstract With the development of proteomics and epigenetics, a large number RNA‐binding proteins (RBPs) have been discovered in recent years, interaction between long non‐coding RNAs (lncRNAs) RBPs has also received increasing attention. It is extremely important to conduct in‐depth research on lncRNA‐RBP network, especially context its role occurrence cancer. Increasing evidence demonstrated that interactions play vital cancer progression; therefore, targeting these could provide new insights for drug discovery. In this review, we discussed how lncRNAs can interact with regulate their localization, modification, stability, activity effects transport, transcription, localization lncRNAs. Moreover, explored regulation influence lncRNAs, RBPs, downstream pathways are related development, such as N6‐methyladenosine (m6A) modification addition, network regulates cell phenotypes, proliferation, apoptosis, metastasis, resistance, immunity, tumor environment, metabolism. Furthermore, summarized therapeutic strategies target network. Although treatments still experimental stage various theories processes being studied, believe may ideas treatment.

Язык: Английский

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Aberrant translation regulated by METTL1/WDR4‐mediated tRNA N7‐methylguanosine modification drives head and neck squamous cell carcinoma progression

Cancer Communications, Год журнала: 2022, Номер 42(3), С. 223 - 244

Опубликована: Фев. 18, 2022

Cancer cells selectively promote the translation of oncogenic transcripts to stimulate cancer progression. Although growing evidence has revealed that tRNA modifications and related genes participate in this process, their roles head neck squamous cell carcinoma (HNSCC) remain largely uncharacterized. Here, we sought investigate function mechanisms transfer RNA (tRNA) N7-methylguanosine (m7 G) modification regulating occurrence development HNSCC.Cell lost-of-function gain-of-function assays, xenograft models, conditional knockout knockin mouse models were used study physiological functions m7 G HNSCC tumorigenesis. expression profiling, mRNA profiling rescue assays performed uncover underlying molecular mechanisms. Single-cell sequencing (scRNA-seq) was conducted explore tumor microenvironment changes.The methyltransferase complex components Methyltransferase-like 1 (METTL1)/WD repeat domain 4 (WDR4) upregulated associated with a poor prognosis. Functionally, METTL1/WDR4 promoted progression metastasis cell-based transgenic models. Mechanistically, ablation METTL1 reduced levels 16 tRNAs, inhibiting subset transcripts, including phosphatidylinositol-3-kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) signaling pathway. In addition, chemical modulators PI3K/Akt/mTOR pathway reversed effects Mettl1 HNSCC. Furthermore, scRNA-seq results altered immune landscape cell-cell interaction between stromal compartment.The found malignancy through global translation, PI3K/AKT/mTOR pathway, alter landscape. could be promising treatment for patients.

Язык: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Язык: Английский

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The regulatory relationship between transcription factor STAT3 and noncoding RNA

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Янв. 3, 2024

Abstract Signal transducer and activator of transcription 3 (STAT3), as a key node in numerous carcinogenic signaling pathways, is activated various tumor tissues plays important roles formation, metastasis, drug resistance. STAT3 considered potential subtarget for therapy. Noncoding RNA (ncRNA) special type transcript. Transforming from “junk” transcripts into molecules involved cell apoptosis, growth, functional regulation, ncRNA has been proven to be closely related epithelial–mesenchymal transition resistance processes cells over the past few decades. Research on relationship between factor ncRNAs attracted increased attention. To date, existing reviews have mainly focused regulation by STAT3; there no review ncRNAs. However, understanding its mechanism comprehensively understand mutual regulatory Therefore, this review, we summarize long noncoding RNA, microRNA, circular possible mechanisms. In addition, provide an update research progress This will new perspective ncRNAs, well targeting or treat diseases such tumors.

Язык: Английский

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Energy metabolism in health and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 18, 2025

Язык: Английский

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Noncoding RNA (ncRNA)-mediated regulation of TLRs: critical regulator of inflammation in tumor microenvironment

Medical Oncology, Год журнала: 2025, Номер 42(5)

Опубликована: Март 31, 2025

Язык: Английский

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Regulation of the Hypoxia-Inducible Factor (HIF) by Pro-Inflammatory Cytokines

Cells, Год журнала: 2021, Номер 10(9), С. 2340 - 2340

Опубликована: Сен. 7, 2021

Hypoxia and inflammation are frequently co-incidental features of the tissue microenvironment in a wide range inflammatory diseases. While impact hypoxia on pathways immune cells has been well characterized, less is known about how stimuli such as cytokines upon canonical hypoxia-inducible factor (HIF) pathway, master regulator cellular response to hypoxia. In this review, we discuss what two major pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β), regulation HIF-dependent signaling at sites inflammation. We report extensive evidence for these directly impacting HIF through transcriptional post-translational levels. conclude that multi-level crosstalk between hypoxic plays an important role shaping nature degree occurring sites.

Язык: Английский

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Cuproptosis-Related lncRNAs are Biomarkers of Prognosis and Immune Microenvironment in Head and Neck Squamous Cell Carcinoma

Frontiers in Genetics, Год журнала: 2022, Номер 13

Опубликована: Июль 22, 2022

Background: Cuproptosis is a new type of cell death that induces protein toxic stress and eventually leads to death. Hence, regulating cuproptosis in tumor cells therapeutic approach. However, studies on cuproptosis-related long noncoding RNA (lncRNA) head neck squamous carcinoma (HNSC) have not been found. This study aimed explore the lncRNAs prognostic marker their relationship immune microenvironment HNSC by using bioinformatics methods. Methods: sequencing, genomic mutations, clinical data TCGA_HNSC were downloaded from The Cancer Genome Atlas. patients randomly assigned either training group or validation cohort. least absolute shrinkage selection operator Cox regression multivariate models used determine model cohort, its independent effect was further confirmed entire cohorts. Results: Based previous literature, we collected 19 genes associated with cuproptosis. Afterward, 783 obtained through coexpression. revealed constructed eight (AL132800.1, AC090587.1, AC079160.1, AC011462.4, AL157888.1, GRHL3-AS1, SNHG16, AC021148.2). Patients divided into high- low-risk groups based median risk score. Kaplan-Meier survival curve overall between statistically significant. receiver operating characteristic principal component analysis demonstrated accurate ability model. Univariate showed score an factor. In addition, establish nomogram predictive power markers. mutation burden significant differences groups. high-risk responded better immunotherapy than those group. We also found scores significantly drug sensitivity HNSC. Conclusion: summary, our identified cuprotosis-related signature as predictor, which may be promising biomarkers for predicting benefit well sensitivity.

Язык: Английский

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Interplay Among Metabolism, Epigenetic Modifications, and Gene Expression in Cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Дек. 24, 2021

Epigenetic modifications and metabolism are two fundamental biological processes. During tumorigenesis cancer development both epigenetic metabolic alterations occur often intertwined together. contribute to reprogramming by modifying the transcriptional regulation of enzymes, which is crucial for glucose metabolism, lipid amino acid metabolism. Metabolites provide substrates modifications, including histone modification (methylation, acetylation, phosphorylation), DNA RNA methylation non-coding RNAs. Simultaneously, some metabolites can also serve as nonhistone post-translational that have an impact on tumors. And enzymes regulate independent their metabolites. In addition, produced gut microbiota influence host Understanding crosstalk among gene expression in may help researchers explore mechanisms carcinogenesis progression metastasis, thereby strategies prevention therapy cancer. this review, we summarize progress understanding interactions between epigenetics.

Язык: Английский

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